Mechanistically, we observed that the formation of the LIFR homodimer mediated by K620 acetylation promotes AKT activation by increasing the interaction between AKT and PDPK1 and increases the expression level of the acetyltransferase GCN5 by blocking CRL4CDT2 E3 ligase complex‐mediated protein degradation via the ubiquitination‐proteasome pathway, thus further increasing the levels of LIFR‐K620 acetylation and promoting PCa progression in PTEN‐null tumours with a positive feedback loop. The gene discussed is AKT1; the disease is posterior cortical atrophy.