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T cells express diverse antigen-specific receptors and are required for eradicating pathogens and transformed cells. T cells expressing CD4 acquire helper effector functions and those expressing CD8 exert cytotoxic activity after antigen recognition. The protein–tyrosine phosphatase, receptor type kappa (PTPRΚ) is mutated in LEC rats, resulting in impaired CD4 + T cell development in the thymus. However, the molecular mechanism of PTPRK controlling CD4 + T cell development remains unclear. We demonstrate herein that inhibition of PTPRK by transducing a dominant negative form of the intracellular domain of PTPRK (PTPRK-ICD-DN) in bone marrow-derived stem cells suppresses the development of CD4 + T cells. The inhibition of PTPRK by PTPRK-ICD-DN or short-hairpin RNA for PTPRK attenuates ERK1/2 phosphorylation in T cells after PMA and ionomycin stimulation. Total thymocytes from LEC rats also showed weaker phosphorylation of ERK1/2 after PMA and ionomycin stimulation than control thymocytes. Furthermore, inhibition of PTPRK by PTPRK-ICD-DN suppressed MEK1/2 and c-Raf phosphorylation, which is required for ERK1/2 phosphorylation. These data indicate that PPTRK positively regulates ERK1/2 phosphorylation, which impacts CD4 + T cell development.