PKD1L3 is a pore-forming subunit of heterotetrameric, non-selective cation channels permeable to Ca²⁺, Na⁺, K⁺, and Mg²⁺ 12. The channel forms a 1:3 stoichiometry with TRPP3, activated by external low pH and Ca²⁺, opening only when extracellular pH rises after acid stimulus removal 12. PKD1L3 interacts with PKD2L1 through transmembrane domains to form candidate sour taste receptors localized to taste pores in circumvallate and foliate papillae 34. This interaction is essential for proper channel trafficking to the cell surface 4. A PKD1L3 splice variant identified in taste buds lacks GPS cleavage sites critical for membrane trafficking 5. Functionally, PKD1L3 may contribute to sour taste perception, though its in vivo role remains unclear and may be indirect 6. Beyond gustatory function, recent genome-wide association studies identified a common PKD1L3 variant significantly associated with IgA nephropathy susceptibility (odds ratio 1.16, P=1.43×10⁻¹¹) and lower haptoglobin protein levels 7, revealing unexpected renal disease relevance. Evolutionary analysis suggests rodents may not be optimal models for PKD1L3 functional studies 8.