RNF5 comprises an N-terminal RING domain and C-terminal TMDs and is regulated by autoubiquitination.170 Misfolded proteins targeted by RNF5 include mutant CFTR,119 solute carrier family 1 member 5 (SLC1A5), and SLC38A2.176 RNF5 also controls the stability of sterol regulatory element-binding protein (SREBP)-cleavage activating protein (SCAP),177,178 JNK-associated membrane protein (JAMP),179 MAVS, an activity that affects the antiviral response,180 and STING, which affects cardiac hypertrophy.181 RNF5 acts in concert with other ubiquitin ligases to ensure optimal ERAD. The gene discussed is SLC1A5; the disease is cardiac hypertrophy.