Germline defects in transcription factors are responsible for a substantial proportion of inherited platelet disorders, underscoring the crucial role of these transcriptional regulators in platelet production and function. Although some of these conditions present with isolated thrombocytopenia, most of them are associated with additional hematological manifestations, such as predisposition to hematologic malignancies or evolution to bone marrow failure, or one of several congenital syndromes, which is relevant for clinical management. The degree of thrombocytopenia varies depending on the underlying genetic disorder and may be associated with a platelet function defect or abnormal granule content. Low megakaryocyte numbers or dysplastic features are frequent findings in the bone marrow, reflecting impaired megakaryocyte development or maturation. Dysregulated gene expression secondary to altered transcriptional regulation has unveiled disease biomarkers which may be relevant for diagnosis. This chapter will cover germline alterations in transcription factors that lead to inherited platelet disorders, describe the pathogenesis and main clinical features associated with each of these conditions, and delineate the diagnostic approach and strategies for patient care.