Proline-rich tyrosine kinase 2 （Pyk2） is a nonreceptor protein tyrosine kinase

which is also known as Ca2 +-dependent tyrosine kinase or related adhesion focal tyrosine kinase.Pyk2 activation exerts a critical regulatory mechanism for various physiological processes including cytoskeleton function

regulation of cell growth and death

modulation of ion channels and multiple signaling events.However

mechanisms underlying the functional diversity of Pyk2 are not clear.A Pyk2 isoform that encodes only part of the C-terminal domain of Pyk2

named as PRNK （Pyk2-related non-kinase）

acts as a dominant-negative inhibitor of Pyk2-dependent signaling by displacing Pyk2 from focal adhesions.Research on functional PRNK probably provides new potential inhibitory tool targeting Pyk2 and makes it possible to explore more of Pyk2 pathological mechanism.PRNK is a promising candidate targeting Pyk2 modulation.This review focuses on the functional investigation of Pyk2 and its structure and localization

including recent research with inhibitory strategies targeting Pyk2 by the method of PRNK.