Transient receptor potential cation channel subfamily C member 4 (TRPC4) and Transient receptor potential cation channel subfamily C member 5 (TRPC5) (TRPC4 (for TRPC4), TRPC5 (for TRPC5))

The TRPC4/5 ion channels are **members of the transient receptor potential (TRP) channel superfamily**, specifically the canonical subfamily C (TRPC), and form tetrameric, non-selective cation channels permeable primarily to sodium (Na⁺), potassium (K⁺), and calcium (Ca²⁺)[1][3][4][6]. These channels assemble as homo- or heterotetramers (including TRPC1/4/5 combinations) and contribute to **receptor-operated and potentially store-operated calcium signaling**, playing crucial roles in neuronal excitability, vascular tone, cellular proliferation, and organellar signaling[3][4]. Their activation is tightly regulated by phospholipids, GPCR-G protein pathways, and direct Gαi protein binding, with unique structural features at the cytoplasmic and pore domains conferring specific gating and pharmacological properties[1][2][3]. TRPC4 and TRPC5 are widely expressed in the brain, cardiovascular system, and various epithelial tissues, and their **dysregulation is implicated in diseases ranging from cardiovascular and renal disorders to psychiatric and neurodegenerative conditions**[4][5]. Pharmacological modulation, including inhibition by selective small molecules and modulation by endogenous phospholipids, has shown promising effects in disease models, particularly for renal cancer and hypertension[2][4][5]. Due to their physiological importance across diverse systems, therapeutic targeting of TRPC4/5 presents both **opportunities and challenges**, including the risk of broad systemic effects and incomplete target specificity[2][5][6].

Other names

Short transient receptor potential channel 4/5TRP-related protein 4/5TRPC4/TRPC5 ion channel complexTRPC4/5 channel

Inhibition of calcium and sodium influx (inhibitors like Pico145, HC-070); Activation/increased Ca²⁺ entry (agonists like Englerin A); Direct modulation by G protein α subunits (Gαi); Indirect modulation via GPCR pathways