Diagram showing the mechanism underlying IT in humans caused by 2 biallelic loss-of-function mutations in the Ptprj gene. Loss of PTPRJ protein caused by biallelic mutations of Ptprj increases phosphorylation of the inhibitory tyrosine on the SRC kinase; reduces activation of SRC and its downstream signaling molecule Syk; weakens GPVI- and thrombin receptor-mediated signaling; impairs SDF1-driven migration of MKs, collagen-induced platelet response, terminal MK maturation, and proplatelet formation; and ultimately results in thrombocytopenia.