Deoxysphingolipids (1-deoxySLs) are neurotoxic sphingolipids associated with obesity and diabetic neuropathy (DN) and have been linked to severity of functional peripheral neuropathies. L-serine supplementation can reduce 1-deoxySL accumulation and improve insulin sensitivity and sensory nerve velocity, but long-term outcomes have not yet been examined. In this work published by CGM investigator Florian Eichler and colleagues, a preclinical model of diabetic neuropathy was treated oral l-serine and longitudinally quantified the extent of functional neuropathy progression. Functional neuropathy and sensory modalities were significantly improved in the treatment group well into advanced stages of disease, however, structural assessments revealed prominent axonal degeneration, apoptosis and Schwann cell pathology, suggesting that neuropathy was ongoing. Thus, despite significant functional improvements, L-serine does not prevent chronic degenerative changes specifically at the structural level, pointing to other processes such as oxidative damage and hyperglycemia that may have additional pathological effects in DN.