TRPC4

TRPC4 (transient receptor potential canonical 4) encodes a non-selective cation channel with moderate Ca²⁺ permeability and functions as a regulator of cellular calcium signaling and membrane excitability^[1][2]. Mechanistically, TRPC4 can be activated downstream of Gα_i-coupled receptors, Gα_q-coupled receptors, and tyrosine kinase pathways, linking extracellular signals to calcium influx and downstream cellular responses^[2]. TRPC4 participates in physiological processes including endothelial permeability, vasodilation, neurotransmitter release, and cell proliferation, highlighting its broad role in signal transduction networks^[2]. In addition, TRPC4-containing channels contribute to calcium homeostasis and have been implicated in cellular migration and neuronal functions in experimental systems^[3]. Disease-associated observations include elevated TRPC4 expression in focal cortical dysplasia type II and tuberous sclerosis complex cortical lesions, supporting continued investigation of TRPC4 in neurological disorders^[3]. Compared with the closely related isoform TRPC5, TRPC4 is a distinct member of the TRPC subfamily, although both channels can participate in related signaling pathways and channel complexes^[4][5]. TRPC4 also forms heteromeric assemblies, including TRPC1/TRPC4-containing channels, which contribute to neuronal and smooth-muscle functions in experimental models^[5]. Structural studies further define TRPC4 as a tetrameric ion channel and provide a framework for mechanistic investigations and pharmacological modulation in future research applications^[1].