Cerebral dopamine neurotrophic factor (CDNF) is an ER-resident protein expressed in the central nervous system. A single dose of a novel CDNF variant can improve motor coordination and increase survival in ALS animal models. It can also delay symptom onset and protect motor neurons in the spinal cord. A novel treatment strategy uses a small molecule linker, S-XL6, to prevent the separation of the SOD1 protein. The experiments confirmed that this treatment method works in mice for a specific mutation of the SOD1 protein associated with familial ALS. Neurofilament light chain (NfL) is being investigated as a potential biomarker for ALS. A new drug is under review by the U.S. Food and Drug Administration that is based on its effects on this molecule. The level of NfL in blood and cerebrospinal fluid has been shown to correlate with the speed and severity of ALS progression. The main focus of the ALS research lies on: (i) addressing the underlying genetic causes through gene therapy and RNA editing; (ii) targeting protein misfolding and aggregation to protect motor neurons; (iii) developing neuroprotective therapies to slow disease progression.