3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) is recruited for ERAD via insulin-induced genes (INSIGs) and exhibits preferential preference for certain ERAD E3 ubiquitin ligases, exemplified by glycoprotein 78 (gp78), chromosome 8 translocation in renal carcinoma (TRC8), and ring finger protein 145 (RNF145).93,94 Tail-anchored membrane proteins with minimal exposure to the ER lumen are recognized by membrane-associated RING C3HC4 finger 6 (MARCHF6) following cleavage of their tail domains by signal peptide peptidase (SPP)95–97 to enable ubiquitination. The gene discussed is MARCHF6; the disease is renal carcinoma.