Primary immunodeficiency disease (PID) is a group of immune disorder caused by gene mutation. It is clinically manifested as recurrent and severe infections especially by specific pathogenic microorganism and often accompanied by auto-immune and high susceptibility to tumors. Cytoskeleton is a system of filaments or fibers that maintains cell shape

support cell’s movement and regulates multiple cellular functions

mainly composed of microtubules

microfilaments and intermediate fibers. On the background of PID and taken Wiskott-Aldrich syndrome (WAS) and DOCK8 deficiency disease as examples

we reviewed on the regulation of WAS protein

DOCK8 as cytoskeleton proteins in cellular immunity

humoral immunity

immune metabolism and their role in nuclear regulation. In addition

we also addressed currently unsolved scientific questions.