Future studies using CSF NfL samples and MR diffusion studies of tissue microstructural integrity, known to be impaired in Wolfram syndrome (Lugar et al., 2016), will help to determine whether the elevated NfL is primarily due to central axonal injury or other aspects of Wolfram syndrome (e.g., diabetes, ER dysfunction) (Piehl et al., 2018; Akamine et al., 2020; van der Plas et al., 2021). This evidence concerns the gene NEFL and Wolfram syndrome.