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PKD can be inherited as a dominant (ADPKD) or a recessive (ARPKD) trait, due to mutations into multiple genes, the most frequent being PKD1, PKD2, and PKHD1. The protein products of these genes (polycystin-1, polycystin-2, and fibrocystin, respectively) have been shown to reside within the primary cilium or to be important for the maturation and trafficking of proteins to the primary cilium. The primary cilium is an organelle protruding from the apical surfaces of renal epithelial cells that functions to sense extracellular signals and translate them into intracellular biochemical information. PKD represents the most common monogenic disorder affecting the kidney and the most common manifestation of human ciliopathies. The precise functions of the polycystin and fibrocystin proteins have not yet been fully elucidated nor have the molecular basis underlying the renal tubule cyst formation that occurs in the absence of sufficient functional expression of these proteins. The genes that are muted in PKD were cloned three decades ago, and since their identification, a wealth of information regarding their structure, cell biology, and physiological properties has been developed. Here, we provide a broad review of the relevant literature and summarize a large body of experimental evidence, while focusing particularly on more recent findings that are poised to change our understanding of the field.<\/jats:p>","DOI":"10.1152\/physrev.00018.2024","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T20:01:16Z","timestamp":1739390476000},"page":"1553-1607","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":46,"title":["Physiologic mechanisms underlying polycystic kidney disease"],"prefix":"10.1152","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4704-4006","authenticated-orcid":false,"given":"Alessandra","family":"Boletta","sequence":"first","affiliation":[{"name":"IRCCS San Raffaele Scientific 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