Checkpoint kinase 2 (CHEK2, Chk2) emerges as an important signal transducer of 
cellular responses to DNA damage and a candidate tumor suppressor whose defects 
contribute to molecular pathogenesis of diverse types of human malignancies, 
both sporadic and hereditary. Here, we briefly outline the molecular properties, 
regulation and physiological role of CHEK2, and review in more detail its 
defects that predispose to tumors, with particular emphasis on familial breast 
cancer. The frequency, penetrance and epidemiological as well as clinical 
significance of the two most studied breast cancer-predisposing variants of the 
CHEK2 gene, 1100delC and I157T, are highlighted in more depth, and additional 
CHEK2 mutations and their cancer relevance are discussed as well. These recent 
findings are considered also from a broader perspective of CHEK2 as the integral 
component of the ataxia telangiectasia-mutated-CHEK2-p53 pathway within the 
genome integrity maintenance system and a barrier against tumor progression. 
Finally, the potential value of information about the CHEK2 status in family 
counseling and optimizition of individualized cancer treatment is discussed.