1PLW, 1PLX, 2LWC, 5E33, 5E3A517918619ENSG00000181195ENSMUSG00000045573P01210P22005NM_006211NM_001135690NM_001002927NM_001348209NP_001129162NP_001002927NP_001335138Proenkephalin (PENK), formerly known as proenkephalin A (since proenkephalin B was renamed prodynorphin), is an endogenous opioid polypeptide hormone which, via proteolyic cleavage, produces the enkephalin peptides met-enkephalin, and to a lesser extent, leu-enkephalin.

[5] Contrarily, Leu-enkephalin] is predominantly synthesized from prodynorphin, which produces three copies of it per cleavage, and no copies of Met-enkephalin.

Other endogenous opioid peptides produced by proenkephalin include adrenorphin,[6] amidorphin,[7] BAM-18,[8] BAM-20P,[9] BAM-22P,[9] peptide B,[10] peptide E,[11] and peptide F.[12] Proenkephalin is produced by the medium spiny neurons of the striatum which undergo neurodegeneration in early stages of Huntington's disease (HD).

PENK[13] and related peptides[14][15] measured in cerebrospinal fluid are proposed as potential biomarkers of disease progression in HD.

Furthermore, PENK has been found associated with acute kidney injury[16] and glomerular filtration rate in steady-state and critically ill patients.