PKD1L3 is a pore-forming subunit of a heterotetrameric, non-selective cation channel permeable to calcium, sodium, potassium, and magnesium. The channel is activated by external low pH and calcium but opens only when extracellular pH rises again after the acid stimulus is removed. PKD1L3 interacts with TRPP3 (also called PKD2L1) through transmembrane domains to form a functional acid-sensing receptor-channel complex at the plasma membrane; the heterotetrameric assembly contains one PKD1L3 and three TRPP3 subunits. PKD1L3 may act as a sour taste receptor in gustatory cells, though its contribution to sour taste perception in vivo remains unclear and may be indirect. A common nonsynonymous variant in PKD1L3 was identified in a genome-wide association study of IgA nephropathy in Han Chinese, showing association with lower haptoglobin protein levels 1. The molecular evolution of PKD1L3 across mammalian species reveals dominant purifying selection, though some sites show evidence of positive selection; rodents display more rapid PKD1L3 evolution than other mammalian lineages, suggesting they may not be optimal models for studying this gene 2. GPS proteolytic cleavage of PKD1L3 is required for trafficking of the PKD1L3/TRPP3 complex to the plasma membrane, and a taste bud-specific splice variant escapes this cleavage, suggesting potentially distinct in vivo functions of uncleaved PKD1L3.