Zinc finger FYVE domain-containing protein 27 (ZFYVE27), also known as SPG33, is a 411 amino acid member of the FYVE-finger family of proteins. The FYVE domain is a cysteine-rich domain of about 70 amino acids that plays a role in the endosomal localization of the FYVE-finger proteins, and a majority of these proteins serve as regulators of endocytic membrane trafficking. ZFYVE27, a multi-pass membrane protein, is an endosomal protein that binds to Spastin, a protein that is primarily involved in microtubule dynamics and severing, vesicular trafficking and endosomal trafficking. Mutations in the gene encoding ZFTVE27 affect neuronal intracellular trafficking in the corticospinal tract and are thought to lead to hereditary spastic paraplegia (HSP), a neurodegenerative disorder, characterized by progressive paralysis of the legs, which is caused by impaired axonal transport. Five isoforms of ZFYVE27 exist as a result of alternative splicing events.