Notably, the S4-S5 linker appears to be a hot-spot for mutations in several TRP channels, including TRPV3 (congenital Olmsted syndrome), TRPV4 (skeletal dysplasia, motor/sensory neuropathies), TRPA1 (familial episodic pain syndrome), and TRPML1 (mucolipidosis type IV) (84). This evidence concerns the gene TRPV3 and familial episodic pain syndrome.