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Transient receptor potential cation channel subfamily P member 3 (TRPP3), also known as Polycystin 2-like 1 (PKD2L1), is a non-selective cation channel belonging to the transient receptor potential (TRP) superfamily [1]. It is primarily recognized for its role as a sour taste sensor in taste bud cells, where it forms a heteromeric complex with PKD1L3 to detect acidic stimuli [2]. Beyond the tongue, TRPP3 is expressed in cerebrospinal fluid-contacting neurons (CSF-cNs) in the spinal cord, acting as a pH-sensitive sensor that monitors the chemical environment of the central nervous system [3]. In these neurons, it contributes to the regulation of motor activity and homeostatic responses to pH changes [4]. While its direct role in human disease is still being elucidated, it is structurally related to PKD2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD) [1]. Pharmacological modulation of TRPP3 is currently limited to non-specific ion channel blockers like amiloride and ruthenium red, making it a subject of interest for developing more selective probes to study sensory transduction and pH regulation [5].
Inhibition of cation conductance through the channel pore
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