Ubiquitin-conjugating enzyme E2S (UBE2S), mitochondrial ubiquitin ligase activator NF-κB (MULAN), ret finger protein 2 (RFP2), breast cancer susceptibility gene 1 (BRCA1), speckle-type POZ protein (SPOP), TNF receptor-associated factor 4 (TRAF4), and F-box and leucine-rich repeat protein 18 (FBXL18), regulate AKT through ubiquitination, affecting its degradation or activation in various cancers (Table 1) [74–76, 78, 79, 232]. Here, UBE2S is linked to cancer.