Also, many 14-3-3-binding 2R-ohnologues are linked to disease, including cancer (the protein kinase B-Raf, E3 ubiquitin ligase mdm2, tumour suppressor p53/TP53 and transcription factor MITF), metabolic disorders (AS160, TBC1D1), movement disorders (ataxin-1, REEP1, protein kinase LRRK2) and developmental RASopathies (disorders linked to the Ras pathway; C-Raf and E3 ubiquitin ligase Cbl) [61–63]. Here, TBC1D4 is linked to metabolic disease.