Periphilin-1 (PPHLN1)

**Periphilin-1 (PPHLN1)** is a nuclear, insoluble protein involved in the formation of the cornified cell envelope during the terminal differentiation of keratinocytes, a key process in maintaining epidermal integrity and barrier function[1][2][6]. It interacts with periplakin and is sequentially incorporated into structures that protect the outer skin layers. Periphilin-1 also serves as a component of the HUSH epigenetic silencing complex, maintaining transcriptional repression at certain genomic loci via the spread of repressive chromatin marks[2][3]. In cancer, a recurrent fusion of FGFR2-PPHLN1 has been identified in intrahepatic cholangiocarcinoma, with evidence that such fusions confer sensitivity to selective FGFR2 inhibition[2]. Overexpression can result in S phase cell cycle arrest by downregulating DNA replication regulators such as CDC7, and periphilin-1 interacts with synphilin-1, implying a possible antiapoptotic or neuroprotective function that may be relevant to Parkinson’s disease[2]. There are currently no drugs directly targeting periphilin-1, but its involvement in fusion proteins and pathway regulation makes it a molecule of growing research interest, particularly in oncology and neurobiology[2][3].

Other names

Periphilin 1PPHLN1HSPC206HSPC232CRCDC7 expression repressorGastric cancer antigen Ga50periphilin-1

Not targeted directly by drugs; when in FGFR2-PPHLN1 fusion, tumors may respond to FGFR2 inhibitors[2]