The Molecular Tête‐à‐Tête between G‐Quadruplexes and the i‐motif in the Human Genome

G‐Quadruplex (GQ) and i‐motif structures are the paradigmatic examples of nonclassical tetrastranded nucleic acids having multifarious biological functions and widespread applications in therapeutics and material science. Recently, tetraplexes emerged as promising anticancer targets due to their structural robustness, gene‐regulatory roles, and predominant distribution at specific loci of oncogenes. However, it is arguable whether the i‐motif evolves in the complementary single‐stranded region after GQ formation in its opposite strand and vice versa. In this review, we address the prerequisites and significance of the simultaneous and/or mutually exclusive formation of GQ and i‐motif structures at complementary and sequential positions in duplexes in the cellular milieu. We discussed how their dynamic interplay Sets up cellular homeostasis and exacerbates carcinogenesis. The review gives insights into the spatiotemporal formation of GQ and i‐motifs that could be harnessed to design different types of reporter systems and diagnostic platforms for potential bioanalytical and therapeutic intervention. The review provides the requisites and implications of mutually exclusive or simultaneous formation of G‐Quadruplex and i‐motif structures in human genome. The comprehensive discussion on the spatiotemporal formation of G‐quadruplex and i‐motif structures gives the insight on their integrated effect in gene‐regulatory functions and cellular homeostasis.