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Currently, nine genes have been identified as causative for <jats:styled-content style=\"fixed-case\">HPS<\/jats:styled-content> in humans. Their pathological effects are attributable to the disrupted biogenesis of lysosome\u2010related organelles (<jats:styled-content style=\"fixed-case\">LRO<\/jats:styled-content>s) existing in multiple cell types or tissues, causing the pigmentory and non\u2010pigmentory defects. This review focuses on the functional aspects of <jats:styled-content style=\"fixed-case\">HPS<\/jats:styled-content> genes in regulating <jats:styled-content style=\"fixed-case\">LRO<\/jats:styled-content> biogenesis and signal transduction. The understanding of these mechanisms expands our knowledge about the involvement of lysosomal trafficking in the targeting of cargoes for constitutive transport, degradation, and secretion. 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