Sp1-like and Krüppel-like factors (KLFs) are zinc-finger proteins essential for eukaryotic transcription. They regulate gene expression by binding to GC-rich promoters and influence cellular functions such as proliferation, apoptosis, differentiation, and cancer. These proteins can act as activators or repressors depending on the promoter and coregulators involved. The Sp1-like/KLF family includes over 21 human proteins, with homologs found in various species. The carboxy-terminal zinc-finger domain is highly conserved and critical for DNA binding, while the amino terminus varies and contains activation or repression domains. Sp1-like/KLF proteins are present in species ranging from nematodes to humans, evolving through multiple gene duplication events. They are involved in growth regulation, development, and disease, with some playing roles in carcinogenesis. The family is divided into subgroups based on sequence and function, with Sp1-Sp6 forming one subgroup and the rest classified as KLFs. Structural features include three zinc-finger motifs, nuclear localization signals, and transcriptional regulatory domains. These proteins interact with coactivators or corepressors to regulate transcription, with some acting as activators and others as repressors. The family's diversity in function highlights the need for further research to understand their roles in cellular processes and disease.Sp1-like and Krüppel-like factors (KLFs) are zinc-finger proteins essential for eukaryotic transcription. They regulate gene expression by binding to GC-rich promoters and influence cellular functions such as proliferation, apoptosis, differentiation, and cancer. These proteins can act as activators or repressors depending on the promoter and coregulators involved. The Sp1-like/KLF family includes over 21 human proteins, with homologs found in various species. The carboxy-terminal zinc-finger domain is highly conserved and critical for DNA binding, while the amino terminus varies and contains activation or repression domains. Sp1-like/KLF proteins are present in species ranging from nematodes to humans, evolving through multiple gene duplication events. They are involved in growth regulation, development, and disease, with some playing roles in carcinogenesis. The family is divided into subgroups based on sequence and function, with Sp1-Sp6 forming one subgroup and the rest classified as KLFs. Structural features include three zinc-finger motifs, nuclear localization signals, and transcriptional regulatory domains. These proteins interact with coactivators or corepressors to regulate transcription, with some acting as activators and others as repressors. The family's diversity in function highlights the need for further research to understand their roles in cellular processes and disease.