Several reviews have covered the molecular details of K63‐linked ubiquitination and its critical role in the regulation of AKT kinase activation and cardiac hypertrophy.71, 72 In this part of review, we have focused on the regulatory function of K63‐linked polyubiquitination in protein kinase activity by taking the serine/threonine kinase AKT as an example (Figure 3). The gene discussed is AKT1; the disease is cardiac hypertrophy.