ATP13A1 is a P5-type ATPase localized to the endoplasmic reticulum (ER) that functions as a membrane protein dislocase, removing mislocalized proteins from the ER membrane 1. It specifically extracts mitochondrial tail-anchored transmembrane proteins and poorly hydrophobic transmembrane domains that have been mistargeted or misfold in the ER through ATP-dependent translocation 2. ATP13A1 recognizes substrates through an unusually large substrate-binding pocket that engages moderately hydrophobic transmembrane sequences via polar interactions, then cooperates with SEC61 for substrate-specific re-translocation and proper folding 3. This enzyme plays a critical quality-control role, correcting inverted topologies contrary to the positive-inside rule and enabling post-translational re-orientation of misfolded multi-spanning membrane proteins 4. Beyond protein folding, ATP13A1 regulates MR1 surface expression, affecting MR1-mediated antigen presentation to mucosal-associated invariant T cells 5. Disease relevance is indicated by ATP13A1 variants identified in intellectual disability families, suggesting its importance for normal neurological development 6. Evolutionary analysis reveals ATP13A1 as the highly conserved P5A clade ortholog of yeast Spf1p, distinct from the diversified mammalian P5B isoforms ATP13A2-5 1.