The pre-mRNA processing factor 19 (PRPF19) is one such substrate recognition receptor for Cullin4B (CUL4B)-based E3 Ligases (19, –, 21), which has been shown to promote ubiquitination and subsequent degradation of mutant ATXN3-polyQ protein, causing spinocerebellar ataxia type 3 (SCA3) cytotoxicity and neurodegeneration (22). The gene discussed is PRPF19; the disease is Spinocerebellar ataxia type 3.