Several mutations in the cargo-binding domain of BicD2 cause devastating brain and muscle developmental diseases, including a subset of spinal muscular atrophy, which is the most common genetic cause of death in infants [20] Several of these point mutations affect binding of BicD2 to the cargoes Nup358, Nesprin-2 and Rab6 in a distinct manner, which may be the underlying molecular mechanism of these congenital diseases [20,49]. Here, RANBP2 is linked to proximal spinal muscular atrophy.