The article provides a comprehensive review of the classical nuclear import pathway, focusing on the interaction between proteins containing classical nuclear localization signals (cNLSs) and the import receptor importin α. The cNLS, characterized by stretches of basic amino acids, is recognized by importin α, which then binds to the β-karyopherin importin β. This heterodimeric complex interacts with the nuclear pore complex and facilitates the translocation of the cargo into the nucleus. The energy for this process is provided by the GTPase Ran, which cycles between GDP and GTP forms to control the binding and release of cargo. The article also discusses the prevalence of cNLSs in eukaryotic cells, estimating that about 45% of proteins have the potential to enter the nucleus via the classical pathway. Additionally, it outlines criteria for confirming the functional importance of a predicted NLS experimentally, emphasizing the need for detailed structural studies and bioinformatics analyses to fully understand nuclear transport mechanisms.The article provides a comprehensive review of the classical nuclear import pathway, focusing on the interaction between proteins containing classical nuclear localization signals (cNLSs) and the import receptor importin α. The cNLS, characterized by stretches of basic amino acids, is recognized by importin α, which then binds to the β-karyopherin importin β. This heterodimeric complex interacts with the nuclear pore complex and facilitates the translocation of the cargo into the nucleus. The energy for this process is provided by the GTPase Ran, which cycles between GDP and GTP forms to control the binding and release of cargo. The article also discusses the prevalence of cNLSs in eukaryotic cells, estimating that about 45% of proteins have the potential to enter the nucleus via the classical pathway. Additionally, it outlines criteria for confirming the functional importance of a predicted NLS experimentally, emphasizing the need for detailed structural studies and bioinformatics analyses to fully understand nuclear transport mechanisms.