TUBB1 encodes β1-tubulin, a major structural component of microtubules that form heterodimers with α-tubulin 1. These microtubules are fundamental cytoskeletal elements organized through GTP-dependent polymerization, with β1-tubulin playing specialized roles in proplatelet formation and platelet shape maintenance through incorporation into the microtubular marginal ring 1. TUBB1 is also expressed in developing thyroid tissue and participates in thyroid migration and hormone secretion 2. Pathogenic TUBB1 variants cause macrothrombocytopenia (isolated, autosomal dominant) with incomplete penetrance and variable phenotypic expression dependent on allelic burden 1. Mutations produce non-functional α/β-tubulin dimers that cannot incorporate into microtubules, impairing proplatelet formation and resulting in reduced platelet counts with increased platelet size 21. TUBB1 variants also cause thyroid dysgenesis leading to congenital hypothyroidism through impaired thyroid development and hormone secretion 23. Additionally, TUBB1 dysfunction disrupts DNA damage responses and diminishes apoptosis, conferring genome instability and increased leukemogenesis risk in inherited thrombocytopenia 4. Elevated TUBB1 expression correlates with favorable prognosis in osteosarcoma and associates with protective effects against osteoarthritis 56. These diverse functions reflect TUBB1's critical structural role across multiple tissues.