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The first requisite is migration of neural crest\u2010derived melanoblasts, which populate various embryonic sites, then differentiate into melanocytes or seed stem cell niches. Differentiation is marked by expression of genes essential for melanogenesis, which takes place in melanosomes and involves conversion of tyrosine into melanin. Melanosome biogenesis requires premelanosome maturation through coordinated delivery of melanogenic enzymes such as tyrosinase (TYR), structural proteins, and transporters that establish an intraluminal environment conducive to melanogenesis. Sorting of proteins through endolysosomal pathways and delivery to melanosomes is facilitated by trafficking protein complexes. Finally, melanin is transferred to keratinocytes to protect against ultraviolet light. Numerous pigment\u2010related disorders result from disruption of these pathways, including Waardenburg syndrome caused by melanoblast migration disruption, oculocutaneous albinism presenting with absent\/reduced melanogenesis, and melanoma resulting from dysregulation of proliferation\/survival. Genetic variants also determine normal color variation, which is pronounced across populations that, historically, lived in different geographical regions. This variation, shaped by genetic factors, environmental influences, and evolutionary pressures, underpins the wide range of pigmentation phenotypes seen today.<\/jats:p>","DOI":"10.1111\/ahg.70003","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:43:16Z","timestamp":1751517796000},"page":"305-320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genetics of Skin, Hair, and Eye Color in Human Pigmentation Disorders"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5501-0343","authenticated-orcid":false,"given":"Prashiela","family":"Manga","sequence":"first","affiliation":[{"name":"The Ronald O. Perelman Department of Dermatology New York University School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-4689","authenticated-orcid":false,"given":"Stacie","family":"Loftus","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch, National Human Genome Research Institute National Institutes of Health  Bethesda Maryland USA"},{"name":"Genetic Disease Research Branch, National Human Genome Research Institute National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2010.00679.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.07.049"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2937-x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10815"},{"key":"e_1_2_9_6_1","volume-title":"Waardenburg Syndrome","author":"Ahmed jan N.","year":"2024"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10095"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-022-02489-y"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-671636"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2001.5251"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng576"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-404350"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade6289"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6.9.880"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12743"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003372"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.04543"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1215555110"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241411289"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.11.3451"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102669"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129273"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.229500"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470987100.ch7"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.1998.tb00324.x"},{"key":"e_1_2_9_26_1","first-page":"1145","article-title":"Mutation in and Lack of Expression of Tyrosinase\u2010Related Protein\u20101 (TRP\u20101) in Melanocytes From an Individual With Brown Oculocutaneous Albinism: A New Subtype of Albinism Classified as \u201cOCA3\u201d","volume":"58","author":"Boissy R. 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