Regardless of the accuracy of the L1CAM hypothesis, we strongly encourage future work characterizing L1CAM-associated EVs and suggest that even if L1CAM is not a definitive marker of neuronal origin, it has been an informative marker with relation to several mood and neuro-related disorders (e.g., Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis [ALS], brain injury, bipolar depression) and that this utility remains regardless of L1CAM’s specificity to neurons/neural tissue [37, 72–75]. This evidence concerns the gene L1CAM and bipolar disorder.