Cholesterol-mediated mycobacteria entry into and survival within macrophages has added a new dimension to Tuberculosis research. The molecular mechanism through which cholesterol initiates this process is still poorly understood. The present study addressed to resolve this mechanism revealed that Mycobacterium tuberculosis possesses cholesterol-specific Receptor 'Ck'-like molecule responsible for mycobacterial entry into macrophages. Further human Receptor-Ck was found to regulate transcriptional expression of a gene that codes for Tryptophan-Aspartate containing coat (TACO) protein responsible for survival of mycobacteria within cells. Based upon these results, we propose that interaction of Receptor-Ck with cholesterol-rich membrane domains helps to create a 'Synaptic-junction' between mycobacteria and macrophage resulting in signalling events that are responsible for mycobacterium entry into and survival within macrophages.