STK38 belongs to the NDR family of serine/threonine protein kinases. NDR kinases require the phosphorylation of conserved Ser/Thr residues for activation. NDR family members have two unique stretches of primary sequence: an N-terminal regulatory (NTR) domain and an insert of several residues between subdomains VII and VIII of the kinase domain. The kinase domain insert functions as an auto-inhibitory sequence (AIS), while binding of the co-activator MOB (Mps-one binder) proteins to the NTR domain releases NDR kinases from inhibition of autophosphorylation. STK38 negatively regulates the activation of MEKK1/2 by direct interaction with the catalytic domain of MEKK1/2. The negative regulation of MEKK1/2 is not due to its phosphorylation by STK38.