Even though it cannot be fully excluded that caspase-3 may also cleave FAK in the process of TRAIL-induced cell death, we here show that cytosolic caspase-8-mediated cleavage of FAK is essential for full apoptosis induction in response to TRAIL-receptor activation, because depletion of caspase-8 fully prevented processing of FAK in MM cells that still expressed downstream caspases. Here, CASP8 is linked to Miyoshi myopathy.