S5a levels are increased in cancer.75, 76, 77 The expression and splicing of S5a is developmentally regulated.17, 78 The ubiquitin/UBL-binding activity of S5a homologues is controlled by stress-dependent mono-ubiquitination in lower organisms.18, 79 S5a is one of three 19S RP subunits that are degraded in a caspase-dependent manner in response to pro-apoptotic agents, possibly as part of a feed forward pro-apoptotic response.80 Ubiquitin receptors are known to be involved in DNA damage responses, members of the UBA/UBL family are DNA damage inducible.81 The gene discussed is PSMD4; the disease is cancer.