PKD2 encodes a transient receptor potential (TRP) cation channel that functions as both a homotetrameric channel and a heteromeric complex with PKD1 1. In the primary cilium, PKD2 functions as a nonselective cation channel with preference for monovalent over divalent cations, facilitating K⁺, Na⁺, and Ca²⁺ influx with low Ca²⁺ selectivity 2. The PKD1/PKD2 heterotetrameric complex exhibits higher Ca²⁺ permeability than PKD2 homomers and acts as a primarily Ca²⁺-permeable channel 1. PKD2 modulates intracellular Ca²⁺ signaling by interacting with other channels including TRPV4, TRPC1, and RYR2 3. Mutations in PKD2 cause autosomal dominant polycystic kidney disease (ADPKD), representing approximately 15% of familial cases 4. PKD2 mutations confer a milder disease phenotype compared to PKD1, with median ESRD onset at 79 years versus 58 years for PKD1 carriers 5. The cryo-EM structure reveals PKD1 and PKD2 form a 1:3 complex with a domain-swapped, noncanonical TRP architecture 6. PKD2 genotype carries 0.2-fold lower ESRD risk than truncating PKD1 mutations, providing important prognostic information for patient stratification and therapeutic interventions 7.