PPP4R3 is a binding partner of the PPP4C catalytic subunit of the PP4 serine/threonine protein phosphatase. PPP4C is structurally related to PP2AC but does not associate with the same regulatory subunits. PPP4C associates with either the PPP4R1 or PPP4R2 regulatory subunit. In addition to PPP4R1 and PPP4R2, PPP4R3 has also been identified as a regulator of PPP4C function. PP4R3 functions with PP4C in the control of recovery from DNA damage. PP4R3 may function by targeting PPP4 to sites of DNA damage via an interaction with Rad53 (CHK2). PP4R3 is the human homolog of the Dictylostelium SMEK (suppressor of MEK). SMEK has been shown to be involved in cell polarization and chemotaxis via an involvement in the MEK1/ERK1 signaling pathway. SMEK also functions by controlling PPP4C localization to nucleus.