Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cellular conditions, and as master transcription factor during integrated stress response (ISR) (By similarity). 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 ISR, ATF4 translation is induced via an alternative ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced ATF4 acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (By similarity). Promotes the transcription of genes linked to amino acid sufficiency and resistance to oxidative stress to protect cells against metabolic consequences of ER oxidation (By similarity). Activates the transcription of NLRP1, possibly in concert with other factors in response to ER stress. Activates the transcription of asparagine synthetase (ASNS) in response to amino acid deprivation or ER stress. However, when associated with DDIT3/CHOP, the transcriptional activation of the ASNS gene is inhibited in response to amino acid deprivation (By similarity). Together with DDIT3/CHOP, mediates programmed cell death by promoting the expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the terminal unfolded protein response (terminal UPR), a cellular response that elicits programmed cell death when ER stress is prolonged and unresolved (By similarity). Together with DDIT3/CHOP, activates the transcription of the IRS-regulator TRIB3 and promotes ER stress-induced neuronal cell death by regulating the expression of BBC3/PUMA in response to ER stress. May cooperate with the UPR transcriptional regulator QRICH1 to regulate ER protein homeostasis which is critical for cell viability in response to ER stress (By similarity). In the absence of stress, ATF4 translation is at low levels and it is required for normal metabolic processes such as 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 (By similarity). Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production. Activates transcription of SIRT4. Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4. 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. 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 (By similarity). Binds DNA as a homodimer and as a heterodimer. Heterodimer; heterodimerizes with CEBPB. Heterodimer; heterodimerizes with DDIT3/CHOP. Interacts with CEP290 (via an N-terminal region) (PubMed:16682973). Interacts with NEK6, DAPK2 (isoform 2) and ZIPK/DAPK3 (By similarity). Interacts (via its leucine zipper domain) with GABBR1 and GABBR2 (via their C-termini) (By similarity). Forms a heterodimer with TXLNG in osteoblasts (By similarity). Interacts (via its DNA binding domain) with FOXO1 (C-terminal half); the interaction occurs in osteoblasts and regulates glucose homeostasis through suppression of beta-cell proliferation and a decrease in insulin production. Interacts with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors (By similarity). Interacts with ABRAXAS2 (By similarity). Interacts with TRIB3, inhibiting the transactivation activity of ATF4. Interacts with DISC1; which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (By similarity). Interacts with EP300/p300; EP300/p300 stabilizes ATF4 and increases its transcriptional activity independently of its catalytic activity by preventing its ubiquitination (By similarity). Colocalizes with GABBR1 in hippocampal neuron dendritic membranes (By similarity). Colocalizes with NEK6 at the centrosome. Recruited to nuclear speckles following interaction with EP300/p300 (By similarity). The BetaTrCP degron motif promotes binding to BTRC when phosphorylated. Ubiquitinated by SCF(BTRC) in response to mTORC1 signal, followed by proteasomal degradation and leading to down-regulate expression of SIRT4. Interaction with EP300/p300 inhibits ubiquitination by SCF(BTRC). Phosphorylation at Ser-242 by RPS6KA3/RSK2 in osteoblasts enhances transactivation activity and promotes osteoblast differentiation (By similarity). Phosphorylated on the betaTrCP degron motif at Ser-215, followed by phosphorylation at Ser-220, Ser-227, Ser-231 and Ser-245, promoting interaction with BTRC and ubiquitination. Phosphorylation is promoted by mTORC1 (By similarity). Phosphorylation at Ser-211 by CK2 decreases its stability. Phosphorylated by NEK6 (By similarity). Hydroxylated by PHD3, leading to decreased protein stability. Belongs to the bZIP family.