Caldesmon is a regulatory actin-, myosin-, and calmodulin-binding protein involved in smooth muscle contraction. Itis a reliable marker of smooth muscle differentiation,labeling both normal smooth muscle tissue and tumors ofsmooth muscle origin (e.g., leiomyomas, leiomyosarcomas,GISTs). It typically shows immunoreactivity in epithelioidmesothelioma but not in ovarian serous carcinoma, makingit a useful marker in differential diagnosis studies. Inresearch, caldesmon is valuable for studying smoothmuscle biology, tumor classification, and mesothelialversus ovarian tumor distinction.