ER membrane-bound sphingomyelin phosphodiesterase 4 (SMPD4) hydrolyses sphingomyelin to ceramide (Krut et al. 2006). Loss-of-function mutations in the SMPD4 gene cause neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies (NEDMABA) (Magini et al., 2019).