Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and acts both as a regulator of normal metabolic and redox processes, and as a master transcription factor during the integrated stress response (ISR). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer (By similarity). Core effector of the ISR, which is required for adaptation to various stress, such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress. During the ISR, ATF4 protein is translated in response to eIF-2-alpha/EIF2S1 phosphorylation caused by stress, and acts as a master transcription factor of stress-responsive genes in order to promote cell recovery. Protects cells against metabolic consequences of ER oxidation by promoting expression of genes linked to amino acid sufficiency and resistance to oxidative stress (By similarity). Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to amino acid deprivation or endoplasmic reticulum (ER) stress. Together with DDIT3/CHOP, mediates ER-mediated cell death by promoting expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the unfolded protein response (UPR) in response to ER stress (By similarity). ATF4 and DDIT3/CHOP activate the transcription of TRIB3 and promote ER stress-induced neuronal cell-death by regulating the expression of BBC3/PUMA. During ER stress response, activates the transcription of NLRP1, possibly in concert with other factors. Activates expression of genes required to promote cell recovery in response to mitochondrial stress. Independently of the ISR, also required for normal metabolic processes: plays a key role in embryonic lens formation, fetal liver hematopoiesis, bone development and synaptic plasticity (By similarity). Acts as a regulator of osteoblast differentiation in response to phosphorylation by RPS6KA3/RSK2: phosphorylation in osteoblasts enhances transactivation activity and promotes expression of osteoblast-specific genes and post-transcriptionally regulates the synthesis of Type I collagen, the main constituent of the bone matrix. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). Activates transcription of SIRT4 (By similarity). Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4 (By similarity). Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes (By similarity). Mainly acts as a transcriptional activator in cellular stress adaptation, but it can also act as a transcriptional repressor: acts as a regulator of synaptic plasticity by repressing transcription, thereby inhibiting induction and maintenance of long-term memory (By similarity). Regulates synaptic functions via interaction with DISC1 in neurons, which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding; (Microbial infection) Binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I.