PKD2L2 encodes polycystin-L2, a six-transmembrane transient receptor potential (TRP) cation channel protein belonging to the polycystin family 1. The protein exhibits lower single-channel conductance compared to related polycystins and functions as a calcium-permeable ion channel component involved in cellular calcium homeostasis 2. PKD2L2 is predicted to form heteromeric complexes with PKD1-like proteins, establishing functional calcium signaling compartments in specialized cellular structures such as primary cilia 3. The gene demonstrates evolutionary conservation across mammalian species under purifying selection, though with weaker constraints than PKD2 and PKD2L1 orthologs, with some transmembrane loop regions showing functional divergence 4. PKD2L2 is expressed in multiple tissues including brain, kidney, testis, and heart, with alternative splicing generating transcript variants 1. Clinically, PKD2L2 variants have been identified in patients with autosomal dominant polycystic kidney disease (ADPKD) and chr5 kidney disease, including novel missense mutations 5. Additionally, PKD2L2 was recently implicated in cardiac conduction disorders through genome-wide association studies, identifying it as a genetic locus associated with atrioventricular block 6.