May play an important role in cardiac development and function. May regulate cardiac conduction and the function of the gap junction protein GJA1. May contribute to the stability and proper localization of GJA1 to cardiac intercalated disk thereby regulating gap junction communication (By similarity). May also play a role in the regulation of mitochondrial respiration and mitochondrial DNA copy number maintenance (PubMed:28295037). Monomer (By similarity). Homodimer (PubMed:26403541). Interacts with GJA1 (By similarity). Interacts weakly with DSP (By similarity). Localizes at the intercalated disk in the ventricular tissue (PubMed:26403541). Predominantly expressed the ventricular tissue (at protein level). Defects in TMEM65 may cause a mitochondrial disorder characterized by a complex encephalomyopathic phenotype. Clinical features includ microcephaly, dysmorphic features, psychomotor regression, hypotonia, growth retardation, lactic acidosis, intractable seizures, dyskenetics movements, without cardiomyopathy (PubMed:28295037). Truncated N-terminus.