Apurinic/apyrimidinic (AP) sites are widespread lesions in genomic DNA, arising from a number of exogenous and endogenous sources. These DNA lesions are highly mutagenic and demand efficient repair. The review is devoted to data on searching for previously unrecognized proteins capable of interaction with intact or cleaved AP sites. We mainly focused on proteins that form Schiff base upon this interaction. It is important to note that the aldehyde at the deoxyribose C1 atom both in intact and cleaved AP sites can readily react with nucleophiles of proteins. In most cases, these interactions results in processing of AP sites although the process is less efficient as compared to classical AP/dRP lyases. The biological role of these interactions in providing of backup pathways of DNA repair processes is discussed.