GP78 is the autocrine motility factor (AMF) receptor. AMF (also known as neuroleukin or NLK) is a tumor-secreted cytokine that induces in vivo invasion and metastasis. AMF induces tumor cell motility in vitro through interaction with GP78. GP78 is distributed evenly across the membranes of normal cells but localizes to the leading and trailing edges of carcinoma cells. In gastric cancer, GP78 surface expression correlates to the pathologic stage and grade of tumor penetration. AMF and GP78 interactions may be involved in a synaptic mechanism for learning and memory formation. GP78 and AMF expression increases in the hippocampi of rats after maze learning. Specifically, GP78 is a RING finger-dependent ubiquitin protein ligase (E3) of the endoplasmic reticulum (ER). GP78 recruits UBC7, an ubiquitin-conjugating enzyme (E2). The E3 activity of GP78 suggests a possible link between metastasis and ubiquitin-mediated protein degradation. In humans, alternative splicing of the GP78 mRNA gives rise to two distinct isoforms, 1 and 2, a type I membrane protein and an integral membrane protein, respectively.