TRPC4 is a calcium-permeable, non-selective cation channel that functions as a receptor-activated ion channel 1. The channel comprises six transmembrane domains with a pore-forming region, existing in multiple splice variants (TRPC4α and TRPC4β being most abundant) 1. Structurally, TRPC4 exhibits a unique architecture with a long pore loop stabilized by a disulfide bond and distinctive cytosolic domains 2. Functionally, TRPC4 can form both homotetrameric and heteromeric channels (e.g., TRPC1/TRPC4), with heteromerization reducing calcium permeability by introducing structural asymmetries in the selectivity filter and lower gate 3. When TRPC1 is incorporated, TRPC4 transitions from a high calcium-selective channel to one preferentially conducting monovalent cations 3. TRPC4 is widely expressed across multiple tissues including neuronal, cardiovascular, and immune cells 1. The channel's properties vary considerably depending on cellular context, activation pathways (Gαq/Gαi-coupled receptors and phospholipase C), and interaction partners like scaffolding proteins and other TRP subunits 1. Physiologically, TRPC4 knockout studies demonstrate roles in vascular tone regulation, endothelial permeability, neurotransmitter release, and social behavior 1. Clinically, TRPC4 dysfunction is implicated in seizure disorders, neurological complications from Zika virus infection, and potentially cardiovascular disease 4.