Penk, short for proenkephalin, is a gene encoding a precursor peptide that is cleaved into enkephalins, which are endogenous opioids. PENK is involved in various biological processes, and its encoded products can interact with opioid receptors to modulate pain, mood, and potentially other physiological functions. The PI3K/Akt signaling pathway has been associated with its functions [1].

In osteosarcoma, bioinformatic analysis showed PENK was downregulated in tumor samples compared to normal human osteoblasts and was identified as a hub gene. Silencing PENK in MG63 cells promoted cell migration, and this effect was partially attenuated by LY294002, indicating PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway [1].

In bladder cancer, DNA methylation of PENK has shown potential as a biomarker. Aberrant methylation of PENK gene sites were identified as potential biomarkers for early detection, and a urine-based mePENK-qMSP test had high sensitivity and specificity in detecting Ta high-grade and advanced tumor stages. Also, a mePENK test for non-muscle-invasive bladder cancer recurrence detection outperformed cytology and the NMP22 test [2,3].

In addition, PENK has been proposed as a biomarker for kidney function, with its plasma concentration correlating with glomerular filtration rate, and it may play a role in kidney regeneration as PENK-A secreted by renal proximal tubules functions as a brake in zebrafish kidney regeneration [4,5].

In an imiquimod-induced psoriasis mouse model, Penk mRNA expression levels increased significantly in the psoriatic skin lesions, suggesting it could be an appropriate marker for psoriasis evaluation [6].

In summary, Penk is involved in multiple biological processes and diseases. Functional studies, especially those using gene-silencing approaches in cell models, have revealed its role in inhibiting osteosarcoma cell migration, its potential as a biomarker for bladder cancer detection and recurrence monitoring, as a biomarker for kidney function, and as a marker for psoriasis. These findings contribute to a better understanding of the biological functions of Penk and provide potential diagnostic and therapeutic implications for related diseases.