Despite that hotspot mutations of PIK3CA (E542K, E545K and H1047R) and AKT1 genes (E17K) are absent in MM [329], the R310C mutation of PIK3CA gene [330] is identified in some cases of MM, as well as ROR2 drives the interaction of MM cells with TME through AKT activation [331]. The gene discussed is ROR2; the disease is Miyoshi myopathy.