Transient receptor potential (TRP) channels are relatively non-selective ion channels that enable the flow of cations down their electrochemical gradient. This enables the increase in intracellular Na⁺ and Ca²⁺ concentrations and ultimately in the cell membrane depolarization, which is important for action potential propagation and muscle contraction¹. They are activated by a broad range of stimuli, namely temperature, voltage, pH, endocrine factors, as well as signaling molecules².

The TRP channel family is composed of 28 members divided into 7 subgroups: TRPV, TRPC, TRPM, TRPA, TRPN, TRPP and TRPML. All members of the TRP family have 6 transmembrane (TM) domains, with the pore between the fifth (S5) and sixth (S6) TM domains. In general, TRP channels enable the passage of either Na⁺ or Ca²⁺ ions with little to no preference.

However, some channels do exhibit some selectivity. Also, TRP channels do not display the positive charges in the S4 voltage-sensing domain like most voltage-sensitive channels, although they do display voltage-dependency³. In addition, the C-terminal, located intracellularly, contains a TRP domain comprising 25 amino acids that are highly conserved between TRP channels. Within the TRP domain, there is a TRP box composed of six amino acids, and TRP box 2 – a proline rich domain^1,3. The TRP domain seems to be responsible for the binding of PIP₂, a phospholipid important for the regulation of channel activity⁴.

TRPP1 (polycystin-2, PC2, PKD2) belongs to the TRPP subfamily along with TRPP3 and TRPP5 proteins, and forms non-selective cation channels with different permeability to various divalent cations^5,6. The cellular localization of TRPP1 has been and still is the subject of a lasting debate. In many cell-types, TRPP1 is retained in the endoplasmic reticulum (ER) where it most likely functions as a Ca²⁺ release channel^7,8, and with the help of cofactors, TRPP2 reaches the plasma membrane and the cilia⁸. TRPP1 expression is widespread and is best characterized for its expression in the kidney where it is developmentally regulated^9,10. In the kidney, it associates with PKD1 (TRPP2) an eleven TM-spanning protein (which does not belong to the TRP superfamily) to form functional channels¹¹. In addition, TRPP1 is identified as one of the genes responsible for autosomal dominant polycystic kidney disease (ADPKD)^5,12.