S165F, a JPH2 mutant that is found in patients with hypertrophic cardiomyopathy, induces hypertrophic skeletal myotubes along with a reduction in RyR1 activity during EC coupling due to a defect in protein kinase C (PKC)-mediated phosphorylation at Ser165 and the subsequent absence of the interaction between JPH2 and TRPC332. The gene discussed is JPH2; the disease is hypertrophic cardiomyopathy.