SPHK2 and plasma cell myeloma: This observation, combined with the previous studies demonstrating that p38MAPK can activate CHOP via phosphorylation of its transactivation domain [48], suggests the potential for ER stress in myeloma cells to connect to the cellular apoptotic machinery through both the IRE1-JNK/p38MAPK pathway and PERK-eIF2α-CHOP signalling, particularly in the context of SK2 inhibition.