Membrane-type 5 matrix metalloproteinase (MT5-MMP) expression is ubiquitous in brain development while restricted to regions of neuroplasticity in adult. In the multipotent NT2 model of neurogenesis and differentiation, MT5-MMP is differentially expressed with significantly higher mRNA levels in the differentiated neuronal hNT cells. MT5-MMP cDNA cloned from NT2 cells unexpectedly revealed a novel sequence (MT5-MMPvar) characterized by a 162 bp deletion. Both transcripts were identified in NT2, hNT and adult human hippocampus. In vitro, MT5-MMPvar translated into a ∼55 kDa protein. It was also detected in NT2, hNT and adult human hippocampus. These results suggest more than one human MT5-MMP transcript may exist in the central nervous system.