The Receptor Interacting Protein Kinase 4 (RIPK4), which is also known as the Protein Kinase C-associated Kinase (PKK), is a key regulator of keratinocyte differentiation.  Mutation of RIPK4 results in Bartsocas-Papas syndrome (BPS), which is associated with severe congenital skin malformations. We have previously identified that most SCC of the skin have decreased RIPK4 mRNA compared to the normal surrounding tissue.  Further, we have shown that RIPK4 is mutated in almost one quarter of cSCCs. RIPK4, due to its central importance in epithelial cells, has been difficult to study as the knockout mouse model, published in 2002, is embryonic lethal and leads to multiple keratinocyte defects.  Our laboratory developed a conditional knockout mouse model that has allowed us to study RIPK4 functions.  Since our initial publication in 2015, we and other laboratories have clearly demonstrated an important role for RIPK4 in keratinocyte differentiation. RIPK4 appears to be a central upstream mediator, involved in a number of key signaling pathways that are important for keratinocyte transformation and SCC.   Our current studies continue to develop novel ways to study RIPK4, develop inhibitors, and exploring this important keratinocyte pathway.

The Function of RIPK4 in Keratinocyte Proliferation and Tumorigenesis.