The onset of DNA replication which is the essential step in the reproduction of any cell requires specific interactions of initiator proteins at defined loci called origins. Although the origin size varies from prokaryotes to eukaryotes, the origin recognition complex which is one of the major players initiating DNA replication across the species is conserved. The orchestrated binding of ORC facilitates DNA melting which in turn is the inception for the duplication of the DNA thus helping to emanate bidirectionally from the origins. The conserved DNA binding domains, ATP regulation and the structural properties of the DNA are the key features of the replication machinery. The ORC proteins exhibit a multifaceted role besides its fundamental role in DNA replication. The ORC mutations leads to various diseases.